Present at the Flood
The Revolution That Revealed Life's Molecular Machinery
The story of the unsung heroes who uncovered the hidden shapes of proteins and DNA.
Introduction: The Dawn of a New Biology
Imagine a world where the intricate molecules of life—the proteins that power our bodies and the DNA that defines our very being—were complete mysteries. Just decades ago, scientists could only guess at their forms. Then, in a stunningly short period, a revolution took place. Between 1933 and 1963, the scientific world was transformed by the birth of structural biology, a field dedicated to visualizing the atomic architecture of life's fundamental building blocks.
This revolution is the subject of Richard E. Dickerson's captivating book, Present at the Flood: How Structural Biology Came About. Dickerson, who was not just a historian but a key participant in these discoveries, provides an intimate account of this pivotal era. He traces the critical path that led to the first three-dimensional glimpses of proteins and DNA, discoveries that became the foundation of all modern molecular biology and medicine 1 .
This was not a calm and orderly progression. It was a torrent of insight, competition, brilliant reasoning, and sometimes happy accidents—a true flood of innovation. Dickerson masterfully captures the nuance, the slight remark that could trigger a cascade of thought, and the very human personalities—their strengths, frailties, and colossal egos—that both propelled and hindered the process of discovery 1 4 .
The Building Blocks of Life: Key Concepts and Theories
To appreciate the revolution, one must understand what was at stake. Before structural biology, scientists knew much about the chemistry of life but were blind to its physical form.
The Central Problem
How do molecules like proteins and DNA, assembled from simple chemical components, carry out the complex processes of life? The answer, pioneers suspected, lay in their three-dimensional structure. Function follows form.
The Tool: X-ray Crystallography
This technique became the primary window into the molecular world. By passing X-rays through crystals of a purified molecule and analyzing the resulting diffraction pattern, scientists could—with immense effort and ingenuity—calculate the position of each atom in the molecule 4 .
The Quest for the First Protein Structure
The race was on to solve the first atomic-level protein structure. This required not just scientific brilliance but also technological and computational innovation. Dickerson himself developed the mathematical basis for refining the "phases" of myoglobin, a crucial step in unlocking the structure of this oxygen-storing protein from whale muscle 1 .
The Intertwined Path to DNA
The discovery of the DNA double helix by James Watson and Francis Crick in 1953 did not happen in isolation. It was deeply synergistic with the work on proteins. The same principles of structural thinking, model-building, and X-ray analysis were being applied in both camps, with personalities and insights clashing and combining to drive science forward 1 .
An In-Depth Look: Cracking the Code of a Protein
The determination of the myoglobin structure by John Kendrew and his team, including Dickerson, stands as a landmark achievement. It was the first time a protein's full atomic arrangement was laid bare. Here is how this pivotal experiment unfolded.
Methodology: A Step-by-Step Journey to a Structure
Crystallize
The purified myoglobin was then coaxed into forming a highly ordered crystal. In this regular, repeating lattice, every molecule is aligned identically, a necessity for producing a clear X-ray diffraction pattern.
Collect Diffraction Data
A crystal was mounted and bombarded with a beam of X-rays. As the rays struck the atoms in the crystal, they scattered, producing a pattern of spots on a detector. This pattern was a fingerprint of the molecule's structure 4 .
Solve the "Phase Problem"
The primary hurdle was the "phase problem"—the diffraction pattern showed the intensity of the spots but lost key information about the waves' alignment. Dickerson's mathematical work on refining these phases was essential to convert the pattern into a readable 3D map 1 .
Results and Analysis: A Glimpse into a New World
When the model was complete, the scientific community was astounded. The structure revealed several profound insights:
- A Tangled Polypeptide Chain
- The Birth of Secondary Structure
- A Protective Hydrophobic Core
- A Specialized Heme Pocket
This was more than just the structure of one protein; it was the first direct proof of how a linear chain of amino acids could fold into a complex, functional machine. It validated the theories of structural biology and opened the door to understanding how all proteins work.
Key Figures in the Structural Biology Revolution
| Scientist | Primary Affiliation | Major Contribution |
|---|---|---|
| Richard E. Dickerson | California Institute of Technology / UCLA | Developed key computational methods for myoglobin; determined atomic structure of B-DNA 1 8 . |
| Max Perutz | MRC Laboratory, Cambridge | Pioneered methods to solve the structure of hemoglobin; mentor to many in the field 1 4 . |
| John Kendrew | MRC Laboratory, Cambridge | Determined the first atomic-resolution structure of a protein (myoglobin) 1 . |
| James Watson & Francis Crick | Cavendish Laboratory, Cambridge | Deduced the double-helix structure of DNA in 1953 1 . |
| Linus Pauling & Robert Corey | California Institute of Technology | Discovered the alpha-helix and beta-sheet structures, the fundamental building blocks of proteins 1 . |
Essential Research Reagents in Early Structural Biology
| Reagent / Material | Function in Research |
|---|---|
| Protein Expression Plasmids | Circular DNA molecules used to instruct bacterial cells (like E. coli) to overproduce large quantities of a specific protein for purification and crystallization 2 . |
| Competent E. coli Cells | Specially prepared bacterial cells that can take up foreign DNA, acting as tiny factories for growing recombinant proteins 2 . |
| Crystallization Solutions | Precise chemical cocktails used to slowly precipitate and organize purified protein molecules into ordered crystals for X-ray diffraction 1 . |
| Chemical Desiccants (e.g., Calcium Sulfate) | Used to dry and preserve biological samples, like bacterial cells expressing enzymes, for stable, long-term storage without a cold chain 2 . |
Major Structural Milestones, 1950-1980
1980
B-Form DNA (Atomic)
Dickerson's high-resolution structure revealed the precise atomic details and variations of the DNA helix 1 .
A Lasting Legacy: The Flood That Reshaped Science
The flood of discovery chronicled by Dickerson did not recede; it permanently altered the landscape of science. The ability to see biological molecules in three dimensions provided a tangible basis for understanding the mechanisms of life. It bridged the gap between chemistry and biology, giving rise to modern molecular biology, rational drug design, and biotechnology 1 .
Modern Molecular Biology
The foundation for understanding life at the molecular level
Rational Drug Design
Designing medications based on molecular structure
Biotechnology
Engineering biological systems for practical applications
Dickerson's book is more than a history; it is a reminder that science is a profoundly human endeavor. It is driven by curiosity, collaboration, and competition, marked by both brilliant insights and stumbles. When Francis Crick first saw Dickerson's atomic-resolution structure of B-DNA, he reportedly exclaimed, "So that's what it looks like!" 1 . This sentiment echoes the experience of an entire generation of scientists—and indeed, all of humanity—who, thanks to this revolutionary period, could finally see the exquisite machinery of life for the first time.